See help. --------------------------------------------------------------- 10: Eur J Cancer. 2000 Aug;36(13 Spec No):1649-60. Hypoxia modulated gene expression: angiogenesis, metastasis and therapeutic exploitation. Dachs GU, Tozer GM. Tumour Microcirculation Group, Gray Laboratory Cancer Research Trust, PO Box 100, Mount Vernon Hospital, HA6 2JR, Northwood, UK. Tumour hypoxia is the result of an imbalance in oxygen supply and demand. It is an adverse prognostic indicator in cancer as it modulates tumour progression and treatment. Many genes controlling tumour biology are oxygen regulated, and new ones are constantly added to the growing list of hypoxia-induced genes. Of specific importance are hypoxia-responsive transcription factors, as they can modulate the expression of numerous different genes. Similarly, growth factors which govern the formation of new blood vessels or which control blood flow are vitally important for both the maintenance of the primary tumour and metastases at distant sites. The purpose of this review is to present an update of selected issues regarding hypoxia-inducible gene expression and how this affects prognosis, angiogenesis and metastasis. It will conclude by discussing gene therapy as one possible means of exploiting tumour hypoxia for the treatment of cancer. Publication Types: Review Review, Tutorial PMID: 10959051 [PubMed - indexed for MEDLINE] ---------------------------------------------------------------
See help. --------------------------------------------------------------- 12: Growth Factors. 2000;17(4):249-68. Gene response of human skin fibroblasts to urokinase- and tissue-type plasminogen activators. Copeta A, Tavian D, Marchina E, De Petro G, Barlati S. Department of Biomedical Sciences and Biotechnologies, University of Brescia, Italy. In a previous work we have reported evidences on the mitogenic activity of urokinase-type and tissue-type plasminogen activator (u-PA, t-PA) on serum-deprived human dermal fibroblasts. In this work we have studied the transcription-dependent changes of some cell-cycle related genes associated with the biological activity of PAs, as well as the possible involvement of protein tyr kinases (PTK) and/or protein kinase C (PKC) in the mitogenic signal transduction. The data obtained demonstrate that the growth factor activity of PAs is associated with: - a rapid transient activation of early response genes, c-fos, c-jun and c-myc; - the subsequent coordinated down-regulation of p53 and p21CIP1; - the constant expression of the MEK1 mRNA in every phase of the cell cycle. Quiescent (G0) cells did not express c-fos, c-jun, c-myc and cyclin A, but upon stimulation with mitogens (fetal calf serum (FCS), u-PA, t-PA) the cyclin A mRNA expression was observed in concomitance with the activation of DNA synthesis. Therefore u-PA, t-PA and FCS similarly modulate the expression of c-fos, c-jun, c-myc, p53, p21CIP1 and cyclin A with only slight differences likely related to the time required for activation of DNA synthesis. The PAs mitogenic stimulation of serum-starved cells was associated with the internalization of their molecules, as revealed by immunostaining. The biological activity of u-PA, t-PA, as well as that of limiting concentration of FCS (1%), was mediated by PTK and PKC. Conversely, PTK, but not PKC, was involved in the activation of the proliferative response of basic fibroblast growth factor in the same experimental conditions. In conclusion, u-PA and t-PA can utilize two different pathways, one depending on PTK and the other on PKC in a way similar to the mitogenic activity induced by low concentration of FCS (1%). PMID: 10801075 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 13: Zentralbl Gynakol. 1999;121(10):473-8. [Value of p53, urokinase plasminogen activator, PAI-1 and Ki-67 in vulvar carcinoma] [Article in German] Hoffmann G, Casper F, Weikel W, Kummerle T, Pollow B, Schaffrath M, Hofmann M, Pollow K. St. Josefs Hospital, Frauenklinik, Wiesbaden. OBJECTIVE: The present study was to measure new prognostic factors including the plasminogen activator urokinase and the plasminogen inhibitor PAI-1, as well as p53 and Ki-67, a marker of proliferation and to compare the clinical value of these in relation to the classic histopathological prognostic factors. MATERIAL AND METHODS: The patient collective included 45 patients with vulvar carcinoma, both primary tumors and recurrences. RESULTS: Highly significant correlations were found for tumor diameter and thickness. According to Kaplan-Meier estimations, the influence of thickness on the prognosis had a p-value of 0.048, while the influence of diameter had a p-value of 0.029. The variable grading was also significantly associated to the probability of survival (p = 0.01). There was no statistically significant correlation between p53 and the parameters grading, degree of keratinization and Ki-67 color index. The correlation between p53 and PAI-1 as well as between UPA and PAI-1 was highly significant. According to the Kaplan-Meier estimations, Ki-67, UPA and PAI-1 had no influence on survival in our group of patients. CONCLUSIONS: For p53, the median value could be used as a divider with the median survival of patients with a p53 below 122 pg/mg protein being 151 months and with a p53 above 122 pg/mg being only 61 months. The corresponding p-value was significant at 0.0201. PMID: 10573820 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 14: Ann Surg. 1999 Aug;230(2):179-84. Protein markers in colorectal cancer: predictors of liver metastasis. Berney CR, Fisher RJ, Yang J, Russell PJ, Crowe PJ. Department of Surgery, Prince of Wales Hospital, University of New South Wales, Randwick, Australia. OBJECTIVE: To assess the significance of the expression of five protein markers (nm23, p53, c-erbB-2, u-PA, and VEGF) to the development of metastasis in colorectal cancer. SUMMARY BACKGROUND DATA: The metastatic cascade is a complex multistep process involving several genetic alterations, angiogenesis activation, and tissue proteolysis. Although the prognosis of colorectal cancer depends on the stage of the tumor, the development of metastasis is difficult to predict. METHODS: Paraffin-embedded specimens of 58 patients who underwent surgery for colorectal cancer were retrospectively analyzed by immunohistochemistry, and the coexpression of these protein markers was related to patient outcome. RESULTS: The risk of developing liver secondaries was correlated with the expression of nm23 protein (p < 0.0001); this was also the case in those patients with Dukes' stage B showing positive nm23 immunostaining (p = 0.006). The determination of the number of positive markers or the cumulative intensity score did not improve the predictive value over and above that of nm23 protein alone. CONCLUSION: Expression of nm23 protein is correlated with the risk of developing liver metastasis. Its evaluation alone may help to determine which patients who have undergone apparently curative resection of a colorectal cancer have an increased risk of liver recurrence, especially those with Dukes' stage B tumors who might be considered for adjuvant chemotherapy. PMID: 10450731 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 15: Eur J Biochem. 1999 Jul;263(2):295-304. Deregulation of the signaling pathways controlling urokinase production. Its relationship with the invasive phenotype. Aguirre Ghiso JA, Alonso DF, Farias EF, Gomez DE, de Kier Joffe EB. Division of Medical Oncology, Department of Medicine, Mount Sinai School of Medicine, New York, USA. aguirj01@doc.mssm.edu We review the evidence in support of the notion that, upon experimental oncogenic transformation or in spontaneous human cancers, mitogenesis and expression of urokinase (uPA) and its receptor (uPAR) are activated through common signaling complexes and pathways. It is well documented that uPA, uPAR or metalloproteinases (MMPs) are overexpressed in tumor cells of mesenchymal or epithelial origin and these molecules are required for tumor invasion and metastasis. Furthermore, oncogenic stimuli, which may render the transformed cells tumorigenic and metastatic in vivo, activate, in a constitutive fashion, the extracellular-regulated kinases (Erk 1 and 2) classical mitogenic pathway and others such as the NH(2)-Jun-kinase (Jnk). Cells from human tumors or oncogene-transformed cells overexpress uPA and uPAR, and also show a sustained activation of the above-mentioned signaling modules. In this paper we show that the classical mitogenic pathway involving Ras-Erk, PKC-Erk or Rac-JNK, among others, is activated by growth factors or endogenously by oncogenes, and constitutively activates uPA and uPAR expression. All the data obtained from human tumors or experimental systems, incorporated into a general model, indicate that oncogenic stimuli lead to the constitutive activation of mitogenesis and uPA and its receptor expression, through the activation of the same classical and nonclassical signaling complexes and pathways that regulate cell proliferation. We also discuss contrasting points of view. For instance, what governs the differential regulation of mitogenesis and the signal that leads to protease overexpression in a way that allows normal cells during physiological events to respond to growth factors, and proliferate without overexpressing extracellular matrix (ECM) proteases? Or how can cells remodel their microenvironment without proliferating? What restrains benign tumors from overexpressing tumor-associated proteases when they certainly have the mitogenic signal fully activated? This may occur by the differential regulation of transcriptional programs and recent reports reviewed in this paper may provide an insight into how this occurs at the signaling and transcriptional levels. Publication Types: Review PMID: 10406935 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 16: Br J Cancer. 1999 May;80(3-4):536-45. Prognostic value of uPA and p53 accumulation measured by quantitative biochemical assays in 1245 primary breast cancer patients: a multicentre study. Broet P, Spyratos F, Romain S, Quillien V, Daver A, Ricolleau G, Rallet A, Toulas C, Asselain B. Departement de Biostatistiques, Institut Curie, Paris, France. The purpose of this retrospective multicentre study was to assess the prognostic value of urokinase plasminogen activator (uPA) and p53 levels in a large series of primary breast cancer, using an automatic quantitative luminometric method. Samples of 1245 operable breast tumours were collected from seven French institutions and patients were followed for a median of 75 months. The median uPA and p53 levels assayed in cytosols by means of the immunoluminometric technique (LIA) were 0.31 and 0.20 ng mg(-1) of protein respectively. In univariate analysis, high levels of uPA and p53 were associated with shorter disease-specific survival, disease-free interval, and distant recurrence-free interval. The 5-year survival rates were 95.5% among patients with uPA values below the 20th percentile, and 77.5% in those with values above the 80th percentile. The 5-year survival rates were 91.0% in patients with p53 values below the 20th percentile, and 77.6% in those with values above the 80th percentile. In multivariate analysis, the risk of disease-related death increased with uPA levels after adjustment for tumour size, histological grade, lymph node involvement, and estrogen receptor status. A high level of uPA was also related to a shorter disease-free interval and distant recurrence-free interval. In node-negative patients, a high level of uPA remained strongly related to the three outcomes. When adjusted for other prognostic factors, p53 was no longer significantly related to the outcomes. Given its rapidity and simple application to routinely prepared cytosols, this LIA may be useful for evaluating the prognostic impact of uPA in primary breast cancer, particularly in node-negative patients. According to our results, the prognostic value of p53 accumulation is limited when uPA is included in multivariate analysis. Publication Types: Multicenter Study PMID: 10408864 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 17: APMIS Suppl. 1999;92:1-29. The plasminogen activation system in lung cancer--with special reference to the prognostic role in "non-small cell lung cancer". Pappot H. Finsen Center, Rigshospitalet, Copenhagen, Denmark. PMID: 10363031 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 18: Jpn J Clin Oncol. 1999 Apr;29(4):187-91. Immunohistochemical analysis of PAI-2 (plasminogen activator inhibitor type 2) and p53 protein in early gastric cancer patients with recurrence: a preliminary report. Kammori M, Kaminishi M, Kobayashi K, Oohara T, Endo H, Takubo K, Hashimoto H. Department of Surgery, University of Tokyo Branch Hospital, Japan. kammori-dis@h.u-tokyo.ac.jp BACKGROUND: High levels of urokinase-type plasminogen activator (u-PA) were demonstrated in gastric carcinomas along with inhibitors of plasminogen activators (PAI-1 and PAI-2). They may influence the ability to invade and metastasize and therefore be of importance to the risk of recurrence of stomach neoplasms after curative operation. This also appears to be the case for p53 mutations and p53 protein overexpression. METHODS: Six patients, all differentiated cancer cases who developed recurrent disease 5-10 years after curative operations for early gastric cancers (recurrence group), were studied in comparison with 49 patients who had no recurrence more than 10 years after similar surgery (control group). The expression of u-PA, PAI-1, PAI-2 and p53 was compared immunohistochemically in the recurrence and control groups. RESULTS: The expression of PAI-2 was significantly more frequent in the recurrence group, being found in five (83.3%) patients vs eight (16.3%) in the control group. p53 was expressed in five (83.3%) patients in the recurrence group and in 15 (30.6%) in the control group; the rate was again significantly higher in the former. CONCLUSION: The results suggest that PAI-2 and p53 expressed in differentiated early gastric cancers are possible indices of the risk of recurrence. PMID: 10340041 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 19: Anticancer Res. 1998 May-Jun;18(3C):2187-97. Prognostic impact of tumor biological factors on survival in node-negative breast cancer. Harbeck N, Dettmar P, Thomssen C, Henselmann B, Kuhn W, Ulm K, Janicke F, Hofler H, Graeff H, Schmitt M. Frauenklinik, Hamburg, Germany. nadia.harbeck@lrz.tu-muenchen.de Tumor biological factors uPA, PAI-1, cathepsin D, S-phase fraction (SPF), MIB1 (Ki-67), p53, and HER-2/neu were assessed in 100 node-negative breast cancer patients. Their prognostic impact on disease-free (DFS) as well as overall survival (OS) was compared to that of traditional factors tumor size, grading, and steroid hormone receptor status. Antigen levels of uPA, its inhibitor PAI-1, and cathepsin D were determined in tumor tissue extracts by immunoenzymatic methods. SPF was determined by flow cytofluorometry, MIB1, p53, and HER-2/neu by immunohistochemistry in adjacent routinely formalin-fixed paraffin sections. Median follow-up in all patients still alive at time of analysis was 76 months. Univariate analysis determined PAI-1 (p = 0.0001), uPA (p = 0.0437), MIB1 (p = 0.0214), and SPF (p = 0.0248) as statistically significant prognostic factors for DFS. In contrast, tumor size, steroid hormone receptor status, grading, p53, HER-2/neu, and cathepsin. D failed to be of prognostic value. In multivariate analysis, including the statistically significant prognostic factors PAI-1, uPA, MIB1, and SPF, only PAI-1 (p = 0.0003, relative risk: 4.7) proved to be of independent statistical significance for DFS. Regarding OS, PAI-1 was the only statistically significant prognostic factor in univariate (p = 0.0001) as well as multivariate analysis (p = 0.0000, relative risk: 7.1). Thus, factors describing the invasive and metastatic capacity of tumor cells (uPA, PAI-1) and factors related to their proliferative activity (SPF, MIB1) provide valuable prognostic information in node-negative breast cancer patients. PMID: 9703782 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 20: Clin Cancer Res. 1998 Jan;4(1):189-96. Prognostic value of p53 and urokinase-type plasminogen activator in node-negative human breast cancers. Peyrat JP, Vanlemmens L, Fournier J, Huet G, Revillion F, Bonneterre J. Laboratoire d'Oncologie Moleculaire Humaine, Centre Oscar Lambret, Lille, France. We measured the levels of p53 and urokinase-type plasminogen activator (uPA) in 634 tumor tissues from 634 different node-negative primary breast cancer patients who underwent locoregional surgery in the Center Oscar Lambret between July 1989 and September 1994. p53 and uPA were assayed using commercially available kits in cytosols prepared for estradiol receptor (ER) and progesterone receptor (PgR) assays. The optimum clinical thresholds were chosen for prognostic studies: 4 ng/ml for p53 and 0.5 ng/ml for uPA. p53 was elevated in 13.7% of the tumors, and uPA was elevated in 27.5% of the tumors; they were negatively related (chi 2 test) to ER and PgR and positively related to histoprognostic grading (HPG) and tumor diameter. uPA was negatively correlated to ER and PgR, and p53 and uPA were positively correlated to each other (P = 0.0001; Spearman test). In the prognostic studies, the 316 patients who did not receive adjuvant chemotherapy were included to avoid treatment interference; this number corresponds to all of the patients operated on between 1989 and 1992. The mean duration of follow-up of living patients was 4 years. In overall survival studies, Cox univariate analyses demonstrated a prognostic value of p53 (P = 0.011; risk ratio, 1.59), uPA (P = 0.038; risk ratio, 2.32), PgR, HPG, and tumor diameter. In Cox multivariate analyses, only HPG had a statistically significant prognostic value. In relapse-free survival studies, univariate analyses demonstrated prognostic values of uPA (P = 0.0011) and of age, and both parameters retained their prognostic value in multivariate analyses (uPA: P = 0.0004). This study demonstrates not only that p53 and uPA have prognostic value but also that these two parameters are linked to other classical clinical, histological, or biological prognostic parameters, as well as to each other. Moreover, because uPA is of prognostic value in multivariate relapse-free survival studies, uPA is an important prognostic factor in node-negative breast cancer patients. PMID: 9516970 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 21: Tumour Biol. 1998;19(2):104-12. Cellular arrangement of human breast cancer cell lines determines hemostatic parameters. Barendsz-Janson AF, Muller AD, Lichtenbeld HH, Van Dam-Mieras MC, Hillen HF. Department of Internal Medicine, University Hospital Maastricht, The Netherlands. a.griffioen@intmed.unimaas.nl Two in vitro models are compared to investigate whether cellular configuration or composition of the matrix in which the cells are cultured influences growth and/or prognostic parameters. T47D, MCF-7 and Hs578T breast cancer cell lines were cultured on two different matrices (agarose and collagen). Growth curves, biological markers (Ki-67, p53 and bcl-2) and the expression of hemostatic parameters were studied. The tested hemostatic parameters were urokinase-type plasminogen activator, tissue-type plasminogen activator and plasminogen activator inhibitor as fibrinolytic parameters and von Willbrand factor, tissue factor, antithrombin III, factor X and factor Xa as coagulation parameters. We found that T47D and MCF-7 formed spheroids in both matrices. Hs578T did not form spheroids; instead, the cells remained single cells in the agarose matrix and grew invasively through the collagen matrix. Expression of the biological markers was similar for spheroids and monolayers. In contrast, a clear difference in expression of hemostatic factors by spheroids and monolayers was found. PMID: 9486561 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 22: Cancer Res. 1997 Jul 15;57(14):3016-25. Human ornithine decarboxylase-overproducing NIH3T3 cells induce rapidly growing, highly vascularized tumors in nude mice. Auvinen M, Laine A, Paasinen-Sohns A, Kangas A, Kangas L, Saksela O, Andersson LC, Holtta E. Department of Pathology, University of Helsinki, Finland. Overexpression of human ornithine decarboxylase (ODC) under the control of strong promoters induces morphological transformation of immortalized NIH3T3 and Rat-1 fibroblasts [M. Auvinen et al., Nature (Lond.), 360: 355-358, 1992]. We demonstrate here that ODC-overproducing NIH3T3 cells are tumorigenic in nude mice, giving rise to rapidly growing, large fibrosarcomas at the site of inoculation. The tumors are capable of invading host fat and muscle tissues and are vascularized abundantly. To disclose the molecular mechanism(s) driving the tumorigenic, invasive, and angiogenic phenotype of the tumors, the ODC-overproducing cell lines and tumor tissues were analyzed for the expression of various potential regulators and mediators of cell proliferation, matrix degradation, and angiogenesis. The tumorigenicity of ODC transformants was associated with elevated polyamine levels and down-regulated growth factor receptors. The invasiveness of the ODC-induced tumors could not be attributed to overexpression of various known extracellular matrix-degrading proteases or matrix metalloproteinases. The induction of the tumor neovascularization proved not to be elicited by vascular endothelial growth factor or basic fibroblast growth factor. Instead, the ODC-overexpressing cells appeared to secrete a novel angiogenic factor(s) that was able to promote migration of bovine capillary endothelial cells in collagen gels and increase the proliferation of human endothelial cells in vitro. In parallel, ODC-transformed cells displayed down-regulation of thrombospondin-1 and -2, the negative regulators of angiogenesis. Thus, the induction of the angiogenic phenotype of the ODC transformants is likely due both to increased expression and secretion of the new angiogenesis-stimulating factor(s) and decreased production and release of the antiangiogenic thrombospondins. PMID: 9230217 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 23: Harefuah. 1996 May 15;130(10):693-9. [Prognostic factors in breast cancer patients] [Article in Hebrew] Roisman I, Peretz T, Reznick AZ, Lifshitz I, Bitterman A, Fares F, Toledano H, Barzilay A, Durst AL. Publication Types: Review Review, Tutorial PMID: 8794662 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 24: Geburtshilfe Frauenheilkd. 1996 Apr;56(4):177-83. [Value of immunohistochemical determination of receptors, tissue proteases, tumor suppressor proteins and proliferation markers as prognostic indicators in primary breast carcinoma] [Article in German] Gohring UJ, Scharl A, Ahr A. Klinik und Poliklinik fur Frauenheilkunde und Geburtshilfe, Universitt Koln. OBJECTIVE: We tested whether immunohistochemical detection of oestrogen and progesterone receptor (ER, PR), the oestrogen-dependent protein pS2, the growth hormone receptors p 185neu and EGF-R, the tumour suppressor protein p53, the tissue proteases Cathepsin D and Urokinase, and the proliferation marker PCNA are of prognostic relevance in breast cancer patients. METHODS: Expression of the proteins listed above was evaluated in formalin-fixed and paraffin-embedded sections of 311 primary breast cancer specimens using modified Avidin-Biotin-Complex methods. Results were correlated to clinical and morphological parameters (age, menopausal status, nodal status, tumour size, tumour grade), and clinical course of disease (complete follow-up in 301 women, median observation time 62 months) utilising univariate and multivariate statistical analyses. RESULTS: If univariate analyses and multivariate regression analyses according to the Cox-model were applied, only Cathepsin D correlated to an elevated risk for recurrence in nodally negative patients (n = 135). In nodally positive women (n = 161), increasing tumour size, tumour grade, lack of ER and PR, expression of p185neu, p53, and PCNA indicated a significantly increased relative risk. CONCLUSIONS: Immunohistochemistry allows the detection of parameters which may indicate prognosis in subgroup of breast cancer patients. PMID: 8682282 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 25: Nucleic Acids Res. 1995 Sep 25;23(18):3710-7. Differential regulation of plasminogen activator and inhibitor gene transcription by the tumor suppressor p53. Kunz C, Pebler S, Otte J, von der Ahe D. Haemostasis Research Unit, Kerckhoff-Klinik, Max-Planck-Institut, Bad Nauheim, Germany. The ability of p53 to activate or repress transcription suggests that its biological function as tumor suppressor is in part accomplished by regulating a number of genes including such required for inhibition of cell growth. We here give evidence that p53 also may regulate genes responsible for the proteolytic degradation of the extracellular matrix, which is considered a crucial feature for local invasion and metastasis of neoplastic cells. An important and highly regulated cascade of such proteolytic events involves the plasminogen activator system. We show that wild-type p53 represses transcription from the enhancer and promoter of the human urokinase-type (u-PA) and the tissue-type plasminogen activator (t-PA) gene through a non-DNA binding mechanism. Oncogenic mutants lost the repressing activity. In contrast, wild-type but not mutant p53 specifically binds to and activates the promoter of the plasminogen activator inhibitor type-1 (PAI-1) gene. Interestingly, one of the p53 mutants (273his) inhibited PAI-1 promoter activity. Our results suggest that altered function of oncogenic forms of p53 may lead to altered expression of the plasminogen activators and their inhibitor(s) and thus to altered activation of the plasminogen/plasmin system during tumor progression. PMID: 7479001 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 26: J Urol. 1992 Apr;147(4):1142-6. Loss of the 17p chromosomal region in a metastatic carcinoma of the prostate. Macoska JA, Powell IJ, Sakr W, Lane MA. Laboratory of Molecular Genetics, Michigan Cancer Foundation, Detroit. Genetic alterations of multiple loci that serve as markers for the induction and progression of disease have been identified in several adenocarcinomas, but not in adenocarcinoma of the prostate. To determine if similar genetic alterations occur in prostate carcinoma and could serve as markers for the extent of clinical disease, we have examined 23 predominantly moderately-differentiated, localized prostate carcinomas and one prostatic dysplasia for changes in the structure and copy number of ten selected genes. These genes include 1) those important to androgen metabolism in the prostate, the androgen receptor and steroid 5 alpha reductase genes; 2) those that map to the 10q (PLAU) and 7q (MET) chromosomal regions found deleted in some prostate carcinomas, and 3) proto-oncogenes (ERBB2, INT2, and MYC) and tumor suppressor gene loci (RB1, TP53 and D17S5) found altered in adenocarcinomas of the breast, colon and lung. Gene alterations were detected in one specimen, a lymph node metastasis from a poorly differentiated tumor. This specimen exhibited loss of heterozygosity for two loci putatively active in tumor suppression, TP53 and D17S5, on the short arm of chromosome 17. This study indicates that gross genetic alterations were not evident and could not be used as markers of tumor development in well- or moderately-differentiated, localized lesions, but that loss of the 17p region may be a useful marker for advanced carcinomas in the prostate. PMID: 1552612 [PubMed - indexed for MEDLINE] ---------------------------------------------------------------